Extracellular Enzyme Activity and Uptake of Carbon and Nitrogen Along an Estuarine Salinity and Nutrient Gradient

Amino acid oxidation (AAO) and peptide hydrolysis (PH) are processes affecting the recycling of organic material and nutrients. We compared extracellular AAO and PH rates to C and N uptake rates along estuarine gradients of salinity, nutrients and productivity in the Pocomoke River, a subestuary of the Chesapeake Bay. This estuary is seasonally depleted in inorganic N, and rich in dissolved organic material (DOM) throughout the year. AAO, PH, and N uptake rates measured in 1999 and 2000 were not limited to particular size fractions measured, or to auto- or heterotrophic groups of organisms. At a station near the turbidity maximum, where chlorophyll a biomass was highest, smaller (\u3c1.2 mum) size-fractions contributed \u3c20% of the AAO in May and up to 80% in August when AAO rates were similar to 10 times lower. Most PH was in the larger (\u3e1.2 mum) size-fraction, except at the least saline station in August of both years. Rates of AAO and PH were not linearly correlated with each other seasonally or spatially. Uptake of NH4+ dominated total N uptake (\u3e50%) at all but the freshwater station, although uptake of organic compounds was measurable at all sites. Rates of dissolved free amino acid uptake, measured using dually labeled compounds, were substantial (up to 11% of the total N uptake) and contributed both C and N for growth. Dual labels unambiguously demonstrated that uptake rates of amino acid C and N were uncoupled; amino acid N was taken up preferentially to amino acid C even when rates were corrected for N uptake from AAO. Conceptual models of DOM cycling should include the realization that enzymatic processes and uptake of DOM occur in both \u27microbial\u27 and larger size fractions. Thus, competition between bacteria and phytoplankton mixotrophs may be an important factor determining the relative uptake of C and N from amino acids and other organic substrates

Anthropogenic drivers for exceptionally large meander formation during the Late Holocene

Large-amplitude meanders may form in low-energy rivers despite generally limited mobility in theses systems. Exceptionally large meanders which even extend beyond the valley sides have developed in the Overijsselse Vecht river (the Netherlands) between ca. 1400 CE (Common Era) and the early 1900s, when channelization occurred. Previous studies have attributed the enhanced lateral dynamics of this river to changes in river regime due to increased discharges, reflecting climate and/or land-use alterations in the catchment. This paper focuses on local aspects that may explain why exceptionally large meanders developed at specific sites. Through an integrated analysis based on archaeological, historical, and geomorphological data along with optically stimulated luminescence dating, we investigated the relative impact of three direct and indirect anthropogenic causes for the local morphological change and enhanced lateral migration rates: (1) lack of strategies to manage fluvial erosion; (2) a strong increase in the number of farmsteads and related intensified local land use from the High Middle Ages onwards; and (3) (human-induced) drift-sand activity directly adjacent to the river bends, causing a change in bank stability. Combined, these factors led locally to meander amplitudes well beyond the valley sides. Lessons learned at this site are relevant for management and restoration of meandering rivers in similar settings elsewhere, particularly in meeting the need to estimate spatial demands of (restored) low-energy fluvial systems and manage bank erosion.</p

IBC CARe Microarray Allelic Population Prevalences in an American Indian Population

Background: The prevalence of variant alleles among single nucleotide polymorphisms (SNPs) is not well known for many minority populations. These population allele frequencies (PAFs) are necessary to guide genetic epidemiology studies and to understand the population specific contribution of these variants to disease risk. Large differences in PAF among certain functional groups of genes could also indicate possible selection pressure or founder effects of interest. The 50K SNP, custom genotyping microarray (CARe) was developed, focusing on about 2,000 candidate genes and pathways with demonstrated pathophysiologic influence on cardiovascular disease (CVD). Methods: The CARe microarray was used to genotype 216 unaffected controls in a study of pre-eclampsia among a Northern Plains, American Indian tribe. The allelic prevalences of 34,240 SNPs suitable for analysis, were determined and compared with corresponding HapMap prevalences for the Caucasian population. Further analysis was conducted to compare the frequency of statistically different prevalences among functionally related SNPs, as determined by the DAVID Bioinformatics Resource. Results: Of the SNPs with PAFs in both datasets, 9.8%,37.2% and 47.1% showed allele frequencies among the American Indian population greater than, less than and either greater or less than (respectively) the HapMap Caucasian population. The 2,547 genes were divided into 53 functional groups using the highest stringency criteria. While none of these groups reached the Bonferroni corrected p value of 0.00094, there were 7 of these 53 groups with significantly more or less differing PAFs, each with a probability of less than 0.05 and an overall probability of 0.0046. Conclusion: In comparison to the HapMap Caucasian population, there are substantial differences in the prevalence among an American Indian community of SNPs related to CVD. Certain functional groups of genes and related SNPs show possible evidence of selection pressure or founder effects

La méthode Padovan® de réorganisation neurofonctionnelle auprès des enfants présentant un trouble de l'acquisition de la coordination : une étude exploratoire mixte

Introduction. Le trouble de l’acquisition de la coordination (TAC) touche environ 6% des enfants. La cause exacte du TAC demeure méconnue, mais les données probantes actuelles issues de la recherche démontrent la présence d’un dysfonctionnement neurologique. La méthode Padovan® de réorganisation neurofonctionnelle est une intervention qui cible ce type de dysfonctionnement et qui est utilisée cliniquement par des thérapeutes, dont des ergothérapeutes, dans divers pays. À ce jour, aucune étude n’a documenté les types de changements possible de cette intervention chez les enfants présentant un TAC. Objectif. Cette étude vise à explorer les types de changement de la méthode Padovan® chez des enfants d’âge scolaire ayant un TAC, en vue de proposer un premier modèle de changement. Méthode. Une étude de cas multiples utilisant une méthode mixte a été réalisée afin d'obtenir des information quant aux capacités des enfants et leur participation dans diverses habitudes de vie. Pour chaque cas (n = 5), les données ont été recueillies à partir d’entrevues semi-dirigées auprès des parents (données qualitatives) et d’analyses documentaires de dossiers ergothérapiques (données qualitatives et quantitatives). Résultats. Les résultats suggèrent des améliorations concernant plusieurs capacités, incluant les activités motrices, l’écriture manuelle et l’estime de soi, ainsi que dans la participation dans les soins personnels, l’éducation et les loisirs. Conclusion. Considérant ces résultats, des études expérimentales devraient être menées pour évaluer l’efficacité de la méthode Padovan® chez les enfants ayant un TAC

Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population

Background: The etiology of pre-eclampsia (PE) is unknown; but it is accepted that normal pregnancy represents a distinctive challenge to the maternal immune system. C-reactive protein is a prominent component of the innate immune system; and we previously reported an association between PE and the CRP polymorphism, rs1205. Our aim was to explore the effects of additional CRP variants. The IBC (Cardiochip) genotyping microarray focuses on candidate genes and pathways related to the pathophysiology of cardiovascular disease. Methods: This study recruited 140 cases of PE and 270 matched controls, of which 95 cases met criteria as severe PE, from an American Indian community. IBC array genotypes from 10 suitable CRP SNPs were analyzed. A replication sample of 178 cases and 427 controls of European ancestry was also genotyped. Results: A nominally significant difference (p value <0.05) was seen in the distribution of discordant matched pairs for rs3093068; and Bonferroni corrected differences (P<0.005) were seen for rs876538, rs2794521, and rs3091244. Univariate conditional logistic regression odds ratios (OR) were nominally significant for rs3093068 and rs876538 models only. Multivariate logistic models with adjustment for mother's age, nulliparity and BMI attenuated the effect (OR 1.58, P = 0.066, 95% CI 0.97–2.58) for rs876538 and (OR 2.59, P = 0.050, 95% CI 1.00–6.68) for rs3093068. An additive risk score of the above two risk genotypes shows a multivariate adjusted OR of 2.04 (P = 0.013, 95% CI 1.16–3.56). The replication sample also demonstrated significant association between PE and the rs876538 allele (OR = 1.55, P = 0.01, 95% CI 2.16–1.10). We also show putative functionality for the rs876538 and rs3093068 CRP variants. Conclusion: The CRP variants, rs876538 and rs3093068, previously associated with other cardiovascular disease phenotypes, show suggestive association with PE in this American Indian population, further supporting a possible role for CRP in PE

Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts

Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of Bacteroidetes, a bloom in Proteobacteria, and the emergence of antibiotic-resistant organisms among the cecal microbiota. When WD-fed mice were administered antibiotics and subjected to 30% liver resection, lethal sepsis, characterized by multiple-organ damage, developed. Notable was the emergence and systemic dissemination of multidrug-resistant (MDR) pathobionts, including carbapenem-resistant, extended-spectrum β-lactamase-producing Serratia marcescens, which expressed a virulent and immunosuppressive phenotype. Analysis of the distribution of exact sequence variants belonging to the genus Serratia suggested that these strains originated from the cecal mucosa. No mortality or MDR pathogens were observed in identically treated mice fed a standard chow diet. Taken together, these results suggest that consumption of a Western diet and exposure to certain antibiotics may predispose to life-threating postoperative infection associated with MDR organisms present among the gut microbiota. IMPORTANCE Obesity remains a prevalent and independent risk factor for life-threatening infection following major surgery. Here, we demonstrate that when mice are fed an obesogenic Western diet (WD), they become susceptible to lethal sepsis with multiple organ damage after exposure to antibiotics and an otherwise-recoverable surgical injury. Analysis of the gut microbiota in this model demonstrates that WD alone leads to loss of Bacteroidetes, a bloom of Proteobacteria, and evidence of antibiotic resistance development even before antibiotics are administered. After antibiotics and surgery, lethal sepsis with organ damage developed in in mice fed a WD with the appearance of multidrug-resistant pathogens in the liver, spleen, and blood. The importance of these findings lies in exposing how the selective pressures of diet, antibiotic exposure, and surgical injury can converge on the microbiome, resulting in lethal sepsis and organ damage without the introduction of an exogenous pathogen

High prevalence and two dominant host-specific genotypes of Coxiella burnetii in U.S. milk

BackgroundCoxiella burnetii causes Q fever in humans and Coxiellosis in animals; symptoms range from general malaise to fever, pneumonia, endocarditis and death. Livestock are a significant source of human infection as they shed C. burnetii cells in birth tissues, milk, urine and feces. Although prevalence of C. burnetii is high, few Q fever cases are reported in the U.S. and we have a limited understanding of their connectedness due to difficulties in genotyping. Here, we develop canonical SNP genotyping assays to evaluate spatial and temporal relationships among C. burnetii environmental samples and compare them across studies. Given the genotypic diversity of historical collections, we hypothesized that the current enzootic of Coxiellosis is caused by multiple circulating genotypes. We collected A) 23 milk samples from a single bovine herd, B) 134 commercial bovine and caprine milk samples from across the U.S., and C) 400 bovine and caprine samples from six milk processing plants over three years.ResultsWe detected C. burnetii DNA in 96% of samples with no variance over time. We genotyped 88.5% of positive samples; bovine milk contained only a single genotype (ST20) and caprine milk was dominated by a second type (mostly ST8).ConclusionsThe high prevalence and lack of genotypic diversity is consistent with a model of rapid spread and persistence. The segregation of genotypes between host species is indicative of species-specific adaptations or dissemination barriers and may offer insights into the relative lack of human cases and characterizing genotypes

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure